The fundamental hypothesis driving this program is that the development and clinical implementation[unreadable] of non-invasive imaging of tumor hypoxia will lead to improved management of patients with solid[unreadable] tumors. However, the hypoxic phenotype is complex and in order to assess the clinical value of noninvasive[unreadable] images of tumor hypoxia, we must first understand the mechanisms operating at a microscopic[unreadable] level that are responsible for the generation of the macroscopic images. For an imaging procedure to[unreadable] successfully discriminate between hypoxic and non-hypoxic tumors at the global level it must also, when[unreadable] examined with sufficient spatial resolution, reflect the differences in hypoxia that exist within tumors at a[unreadable] microscopic level. There is no single "gold standard" technique for determining tumor hypoxia that can be[unreadable] used to verify all the others - each technique has its own particular strengths and weaknesses. This[unreadable] means we must use multiple techniques with the goal of achieving a consensus and require a systematic[unreadable] approach to registration, correlation and validation. The role of the tumor and radiation biology core is to[unreadable] provide a set of model systems and assays that enable tumor hypoxia to be studied and the components[unreadable] of the multi-modality imaging approach to be compared with relevant biological indices.[unreadable] The specific tasks of this core are to:[unreadable] 1. characterize tumor cell lines in terms of their oxygen-dependent behavior in-vitro and tumor[unreadable] morphology in-vivo and identify suitable model systems for study by the research projects;[unreadable] 2. generate and characterize appropriate tumor cell lines stably transfected with the TKeGFP fusion[unreadable] gene expressed either constitutively or under the control of a hypoxia response element;[unreadable] 3. implement and validate immunohistochemical methods of detecting endogenous markers related to[unreadable] tumor hypoxia and exogenous tracers of tumor hypoxia;[unreadable] 4. implement and validate assays of radiobiological damage in tumor samples and sections;[unreadable] 5. optimize the use of invasive oxygen probes to measure intratumoral oxygen tension.